Neural circuitry and mechanisms of waiting impulsivity: relevance to addiction

Abstract

Impatience-the failure to wait or tolerate delayed rewards (e.g. food, drug and monetary incentives)-is a common behavioural tendency in humans. However, when rigidly and rapidly expressed with limited regard for future, often negative consequences, impatient or impulsive actions underlie and confer susceptibility for such diverse brain disorders as drug addiction, attention-deficit hyperactivity disorder (ADHD) and major depressive disorder. Consequently, 'waiting' impulsivity has emerged as a candidate endophenotype to inform translational research on underlying neurobiological mechanisms and biomarker discovery for many of the so-called impulse-control disorders. Indeed, as reviewed in this article, this research enterprise has revealed a number of unexpected targets and mechanisms for intervention. However, in the context of drug addiction, impulsive decisions that maximize short-term gains (e.g. acute drug consumption) over longer-term punishment (e.g. unemployment, homelessness, personal harm) defines one aspect of impulsivity, which may or may not be related to rapid, unrestrained actions over shorter timescales. We discuss the relevance of this distinction in impulsivity subtypes for drug addiction with reference to translational research in humans and other animals. This article is part of the theme issue 'Risk taking and impulsive behaviour: fundamental discoveries, theoretical perspectives and clinical implications'.

Keywords: basal ganglia; dopamine; endophenotypes; nucleus accumbens; prefrontal cortex; substance use disorder.

Figure 1.

Measurement of waiting impulsivity endophenotypes in humans. (a) The Four-Choice Serial Reaction Time Task (4CSRTT) is a direct translation of the rodent Five-Choice Serial Reaction Time Task (5CSRTT), which measures the ability to monitor and restrain responding in the face of unpredictable visual targets. The task is administered on a touch-sensitive computer. To initiate a trial, participants are instructed to press and hold down with their index finger the space bar on the computer key board, which results in four white squares appearing on the black computer screen. Following a pre-set cue-trial interval, the target stimulus (a green circle) appears briefly in one of the four squares. Participants are instructed to immediately release the space bar with the same finger and touch the screen in the square where the target had appeared. Correct responses are reinforced by a hypothetical monetary reward. Missed or delayed responses are punished by the deduction of money for that trial. Premature responses, where participants responded prior to the onset of the visual target, however, were not punished. (b) The Monetary Choice Questionnaire qualifies the decline of the value of a monetary reward with increasing delay of its delivery. It consists of a fixed set of 27 choices between a smaller immediate and postponed monetary rewards. The key outcome measure k reflects the degree to which the value of the reward is affected by delay (i.e. higher k values indicate steeper discounting of delayed rewards).

Figure 2.

Dissociation between the neural substrates underpinning waiting and stopping impulsivity (adapted from Clark et al. [21] with permission). Stopping impulsivity, which requires the cancellation of an ongoing motor response, frequently measured using the stop-signal task, is dependent on dorsostriatal mechanisms. By contrast, waiting impulsivity describes a failure to inhibit the initiation of an inappropriate response that is based on incorrect predictions of time or probability. Waiting impulsivity relies on the functional integrity of the ventral striatum. Data collected from 28 healthy control participants and 28 matched cocaine-addicted patients show prolonged response latencies for both going and stopping in the cocaine group. On the 4CSRTT, cocaine-addicted individuals exhibit a tendency to respond more prematurely or incorrectly (commission errors) relative to their healthy peers. In a decision-making context, using the Cambridge Gamble Task (www.cambridgecognition.com) cocaine-addicted individuals make disadvantageous choices as they are less likely to play safe (select the most likely option), but are not more prone to gamble more on the risky options. NAcc, nucleus accumbens; VTA, ventral tegmental area.